The current epidemic of childhood obesity is associated with an increased risk for type 2 diabetes (T2D) and cardiovascular disease (CVD). This proposal will evaluate the role of inflammation and oxidative stress (OS) as potential underlying mechanisms leading to insulin resistance (IR) and increased risk for atherosclerosis in obese (O) children. The candidate is a junior faculty member in the division of Pediatric Endocrinology at the University of Virginia (UVA) who has performed a preliminary study on this topic over the last year as a fellow. She is in the Clinician Investigator tenure track, this will allow her at least 75% of protected research time. This award will allow her to continue her research career development by consolidating her knowledge of the different aspects involved in clinical research and by deepening her knowledge of basic research tools available to explore the molecular mechanisms of disease. UVA offers a Multidisciplinary Clinical Investigator Training Program. Through this program the candidate will attend courses appropriate to complete her training including biostatistics, ethics and epidemiology. She will also have the opportunity to interact with multiple accomplished clinician investigators and scientists from the divison of Endocrinology and the Cardiovascular (CV) Research Center. Her long term career goals are to continue in an academic position to become a leader in the field of pediatric diabetes research with the ultimate goal of improving patient care and minimizing the comorbidities associated with childhood obesity and diabetes. The proposed research will :1 ) determine if O children exhibit a state of low-grade chronic inflammation and increased OS compared with lean (L) children;2) determine if O children exhibit increased CV risk as evidenced by increased soluble cell adhesion molecules, increased monocyte surface expression of adhesion molecules and endothelial dysfunction. Furthermore, we will determine if differences observed between O and L children are related to IR; and 3) through a 6-month intervention program we will determine if metformin or lifestyle modification, known to improve insulin sensitivity, will lead to an associated improvement on inflammation and OS in O children. Findings from this study may help to identify new risk predictors that can be used in the evaluation of obese children and it may also help to develop new therapeutic approaches for the major issue of preventing T2D and CVD.